Excess Calcium, Magnesium and Phosphorus Deposition in the Epigastric Artery of Dialysis Patients Undergoing Renal Transplantation

ABSTRACT Objective: Vascular calcification contributes to cardiovascular disease on dialysis patients. Arterial mineral content is modified but not well defined. We aim to define what is the concentration of calcium, magnesium and phosphorus in the epigastric artery of adult dialysis patients undergoing renal transplantation. Methods: All renal allograft recipients who underwent surgery at our centre between May 2003 and December 2005 and consented to be taken small samples of epigastric artery were included in our cross-sectional study. Histological, radiological and spectrometric methods were used to measure vascular calcification, deposits and concentrations of calcium, phosphorus and magnesium in epigastric artery, which were correlated with clinical and biochemical characteristics. Mineral vascular content was compared with corresponding samples from cadaveric renal donors free from renal disease (control group). Results: Calcium and magnesium concentrations in epigastric artery were much higher in recipients (n = 100) than in donors (n = 30). Histologically confirmed calcifications were more frequent in recipients. Calcium and magnesium content in epigastric artery were correlated directly with recipient age, pre-transplant serum P and Ca × P product. A high content of calcium and magnesium in this artery was observed in recipients with media and intimal calcification. Multivariate logistic regression showed that dialysis vintage > 3.5 years and calcium concentration in epigastric artery ≥ 4500 mg/kg wet weight were independent predictors of histological calcification. Conclusion: Excess mineral deposition is observed in the epigastric artery of dialysis patients, where the recipient's age, serum P, Ca × P product and time on dialysis play a decisive role.

Blood biomarkers and prognosis of amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: The objective was to assess the ability of eight commonly measured blood markers to serve as prognostic biomarkers in amyotrophic lateral sclerosis (ALS). METHODS: A cohort study was conducted of 399 individuals with newly diagnosed ALS between 2006 and 2011 in Stockholm, Sweden. Information on eight blood markers, including creatinine, albumin, haemoglobin, C-reactive protein (CRP), glucose, potassium, sodium and calcium, measured at or after the date of ALS diagnosis, was collected. The Cox regression model and joint model were used to explore the associations between biomarkers and risk of mortality. RESULTS: The mean age at ALS diagnosis was 66.25 years and 58% of the patients were male. A lower than median level of serum creatinine [hazard ratio (HR) 1.67; 95% confidence interval (CI) 1.31-2.12] or albumin (HR 1.49, 95% CI 1.13-1.96) whereas a higher than median level of log-transformed CRP (HR 1.33, 95% CI 1.04-1.71) or glucose (HR 1.34, 95% CI 1.01-1.78) at baseline was associated with a higher mortality risk. Taking all available measurements after ALS diagnosis into account, an association was found between per standard deviation (SD) decrease in serum creatinine (HR 2.23, 95% CI 1.81-2.75) or albumin (HR 1.83, 95% CI 1.43-2.36) as well as per SD increase of log(CRP) (HR 1.96, 95% CI 1.58-2.43) or glucose (HR 1.61, 95% CI 1.21-2.12) and a higher mortality risk. No clear association was found for haemoglobin, potassium, sodium or calcium. CONCLUSIONS: This study suggests that serum creatinine, albumin, CRP and glucose measured at the time of ALS diagnosis as well as their temporal changes after ALS diagnosis could serve as additional prognostic biomarkers for ALS. Their values in routine clinical practice and clinical trials of ALS need to be investigated further.

Lipophilic index, kidney function, and kidney function decline.

BACKGROUND AND AIMS: Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. METHODS AND RESULTS: Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended re-examination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction ≥30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m2 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m2, p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). CONCLUSIONS: A high LI was associated with lower kidney function, kidney function decline, and CKD progression.

Excess protein intake relative to fiber and cardiovascular events in elderly men with chronic kidney disease.

BACKGROUND AND AIMS: The elevated cardiovascular (CVD) risk observed in chronic kidney disease (CKD) may be partially alleviated through diet. While protein intake may link to CVD events in this patient population, dietary fiber has shown cardioprotective associations. Nutrients are not consumed in isolation; we hypothesize that CVD events in CKD may be associated with dietary patterns aligned with an excess of dietary protein relative to fiber. METHODS AND RESULTS: Prospective cohort study from the Uppsala Longitudinal Study of Adult Men. Included were 390 elderly men aged 70-71 years with CKD and without clinical history of CVD. Protein and fiber intake, as well as its ratio, were calculated from 7-day dietary records. Cardiovascular events were registered prospectively during a median follow-up of 9.1 (inter-quartile range, 4.5-10.7) years. The median dietary intake of protein and fiber was 66.7 (60.7-71.1) and 16.6 (14.5-19.1) g/day respectively and the protein-to-fiber intake ratio was 4.0 (3.5-4.7). Protein-to-fiber intake ratio was directly associated with serum C-reactive protein levels. During follow-up, 164 first-time CVD events occurred (incidence rate 54.5/1000 per year). Protein-fiber intake ratio was an independent risk factor for CVD events [adjusted hazard ratio, HR per standard deviation increase (95% confidence interval, CI) 1.33 (1.08, 1.64)]. Although in opposing directions, dietary protein [1.18 (0.97, 1.44)], dietary fiber alone [0.81 (0.64, 1.02)], were not significantly associated with CVD events. CONCLUSIONS: An excess of dietary protein relative to fiber intake was associated with the incidence of cardiovascular events in a homogeneous population of older men with CKD.

Relationship between renal function and renal volume in autosomal dominant polycystic kidney disease: cross-sectional study.

OBJECTIVE: To determine in patients with autosomal dominant polycystic kidney disease the relationship between total renal volume (the sum of both kidneys, TRV) as measured by magnetic resonance and renal function; and its behaviour according to sex and the presence of arterial hypertension, hypercholesterolaemia and hyperglycemia. METHOD: Cross-sectional study including patients with autosomal dominant polycystic kidney disease who underwent periodic reviews at Nephrology external consultations at Hospital de las Nieves de Granada, and who underwent an magnetic resonance to estimate renal volume between January 2008 and March 2011. RESULTS: We evaluated 67 patients (59.7% women, average age of 48±14.4 years) and found a significant positive association between TRV and serum creatinine or urea, which was reversed compared with estimated glomerular filtration by MDRD-4 and Cockcroft-Gault. Women showed an average serum creatinine level and a significantly lower TRV level compared with males. Subgroups affected by arterial hypertension and hyperuricemia presented average values for serum creatinine and urea, higher for TRV and lower for estimated glomerular filtration. The hypercholesterolaemia subgroup showed higher average values for urea and lower for estimated glomerular filtration, without detecting significant differences compared with TRV. CONCLUSION: The volume of polycystic kidneys measured by magnetic resonance is associated with renal function, and can be useful as a complementary study to monitor disease progression. The presence of arterial hypertension, hyperuricemia or hypercholesterolaemia is associated with a poorer renal function.

Dietary protein-fiber ratio associates with circulating levels of indoxyl sulfate and p-cresyl sulfate in chronic kidney disease patients.

BACKGROUND AND AIMS: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are uremic toxins derived solely from colonic bacterial fermentation of protein. Dietary fiber may counteract this by limiting proteolytic bacterial fermentation. However, the influence of dietary intake on the generation of IS and PCS has not been adequately explored in chronic kidney disease (CKD). METHODS AND RESULTS: This cross-sectional study included 40 CKD participants (60% male; age 69 ± 10 years; 45% diabetic) with a mean estimated glomerular filtration rate (eGFR) of 24 ± 8 mL/min/1.73 m(2), who enrolled in a randomized controlled trial of synbiotic therapy. Total and free serum IS and PCS were measured at baseline by ultra-performance liquid chromatography. Dietary intake was measured using in-depth diet histories collected by a dietitian. Associations between each toxin, dietary fiber (total, soluble and insoluble), dietary protein (total, and amino acids: tryptophan, tyrosine and phenylalanine), and the protein-fiber index (ratio of protein to fiber) were assessed using linear regression. Dietary fiber was associated with free and total serum PCS (r = -0.42 and r = -0.44, both p < 0.01), but not IS. No significant association was observed between dietary protein and either toxin. The protein-fiber index was associated with total serum IS (r = 0.40, p = 0.012) and PCS (r = 0.43, p = 0.005), independent of eGFR, sex and diabetes. CONCLUSION: Dietary protein-fiber index is associated with serum IS and PCS levels. Such association, beyond fiber and protein alone, highlights the importance of the interplay between these nutrients. We speculate that dietary modification towards a lower protein-fiber index may contribute to lowering IS and PCS.

Epicardial fat accumulation, cardiometabolic profile and cardiovascular events in patients with stages 3-5 chronic kidney disease.

BACKGROUND: It has been hypothesized that epicardial adipose tissue (EAT) exerts pathogenic effects on cardiac structures. We analysed the associations between EAT and both cardiovascular (CV) disease risk factors and CV events in patients with chronic kidney disease (CKD). PATIENTS AND METHODS: We included 277 nondialysed patients [median age 61, interquartile range (IQR) 53-68 years; 63% men] with stages 3-5 CKD in this cross-sectional evaluation. EAT and abdominal visceral adipose tissue (VAT) were assessed by computed tomography. Patients were followed for median 32 (IQR 20-39) months, and the composite of fatal and nonfatal CV events was recorded. RESULTS: With increasing EAT quartiles, patients were older, had higher glomerular filtration rate, body mass index, waist, VAT and coronary calcification, higher levels of haemoglobin, triglycerides, albumin, C-reactive protein and leptin and higher prevalence of left ventricular hypertrophy and myocardial ischaemia; total and high-density lipoprotein cholesterol, 25-hydroxy-vitamin D and 1, 25-dihydroxy-vitamin D progressively decreased. Associations between EAT and cardiac alterations were not independent of VAT. During follow-up, 58 CV events occurred. A 1-SD higher EAT volume was associated with an increased risk of CV events in crude [hazard ratio (HR) 1.41, 95% confidence interval (CI) (1.12-1.78) and adjusted (HR 1.55, 95% CI 1.21-1.99) Cox models. However, adding EAT to a standard CV disease risk prediction model did not result in a clinically relevant improvement in prediction. CONCLUSION: Epicardial adipose tissue accumulation in patients with CKD increases the risk of CV events independent of general adiposity. This is consistent with the notion of a local pathogenic effect of EAT on the heart or heart vessels, or both. However, EAT adds negligible explanatory power to standard CV disease risk factors.

Dietary acid load, kidney function, osteoporosis, and risk of fractures in elderly men and women.

SUMMARY: Because kidney dysfunction reduces the ability to excrete dietary acid excess, we hypothesized that underlying kidney function may have confounded the mixed studies linking dietary acid load with the risk of osteoporosis and fractures in the community. In a relatively large survey of elderly men and women, we report that dietary acid load did neither associate with DEXA-estimated bone mineral density nor with fracture risk. Underlying kidney function did not modify these null findings. Our results do not support the dietary acid-base hypothesis of bone loss. INTRODUCTION: Impaired renal function reduces the ability to excrete dietary acid excess. We here investigate the association between dietary acid load and bone mineral density (BMD), osteoporosis, and fracture risk by renal function status. METHODS: An observational study was conducted in 861 community-dwelling 70-year-old men and women (49% men) with complete dietary data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The exposure was dietary acid load as estimated from 7-day food records by the net endogenous acid production (NEAP) and potential renal acid load (PRAL) algorithms. Renal function assessed by cystatin C estimated glomerular filtration rate was reduced in 21% of the individuals. Study outcomes were BMD and osteoporosis state (assessed by DEXA) and time to fracture (median follow-up of 9.2 years). RESULTS: In cross-section, dietary acid load had no significant associations with BMD or with the diagnosis of osteoporosis. During follow-up, 131 fractures were validated. Neither NEAP (adjusted hazard ratios (HR) (95% confidence interval (CI)), 1.01 (0.85-1.21), per 1 SD increment) nor PRAL (adjusted HR (95% CI), 1.07 (0.88-1.30), per 1 SD increment) associated with fracture risk. Further multivariate adjustment for kidney function or stratification by the presence of kidney disease did not modify these null associations. CONCLUSIONS: The hypothesis that dietary acid load associates with reduced BMD or increased fracture risk was not supported by this study in community-dwelling elderly individuals. Renal function did not influence on this null finding.

Epicardial fat accumulation, cardiometabolic profile andcardiovascular events in patients with stages 3–5 chronickidney disease

Cordeiro AC, Amparo FC, Oliveira MAC,Amodeo C, Smanio P, Pinto IMF, Lindholm B,Stenvinkel P, Carrero JJ (Karolinska Institutet,Stockholm, Sweden; Dante Pazzanese Institute ofCardiology, S~ao Paulo; Dante Pazzanese Institute ofCardiology, S~ao Paulo; Dante Pazzanese Instituteof Cardiology, S~ao Paulo; Dante Pazzanese Instituteof Cardiology, S~ao Paulo, Brazil). Epicardialfat accumulation, cardiometabolic profile andcardiovascular events in patients with stages3–5 chronic kidney disease.

Prevalence of sarcopenia in elderly maintenance hemodialysis patients: the impact of different diagnostic criteria.

UNLABELLED: The prevalence of sarcopenia on elderly maintenance hemodialysis (MHD) has been scarcely investigated. OBJECTIVES: To investigate the prevalence of decreased muscle mass and strength alone or combined (true sarcopenia) in elderly patients on MHD according to different methods and cutoff limits. Additionally, we evaluated the agreement between dual energy x-ray absorptiometry (DXA) and surrogate methods for the assessment of muscle mass. DESIGN: Observational and cross-sectional study. PARTICIPANTS: Non-institutionalized 102 elderly (age > 60 years) patients on MHD. MEASUREMENTS: Sarcopenia was considered when the patient fit one criteria for low muscle mass assessed by DXA, bioelectrical impedance (BIA), sum of skinfold thicknesses (SKF), calf circumference and mid-arm muscle circumference (MAMC) and one for low muscle strength evaluated by handgrip dynamometer. RESULTS: Decreased muscle strength was found in 85% of the patients. The prevalence of decreased muscle mass varied from 4 to 73.5% and of sarcopenia (decreased muscle mass and strength combined) from 4 to 63%, depending on the method and cutoff limit applied. A small percentage of patients (2 to 15%) were classified as sarcopenic by more than one diagnostic criteria. The agreement between DXA and the surrogate methods to assess muscle mass showed better kappa coefficients with BIA (r=0.36; P<0.01) and SKF (r=0.40; P<0.01). CONCLUSION: A wide prevalence of sarcopenia is observed depending on the method and cutoff limit applied. This may limit extrapolate on to clinical practice. BIA and SKF were the surrogate methods to assess muscle mass with the best concordance with DXA in elderly MHD patients.

Serum fatty acid patterns, insulin sensitivity and the metabolic syndrome in individuals with chronic kidney disease.

OBJECTIVES: The causes of the multiple metabolic disorders of individuals with chronic kidney disease (CKD) are not fully known. We investigated the relationships between dietary fat quality, the metabolic syndrome (MetS), insulin sensitivity and inflammation in individuals with CKD. SUBJECTS: Two population-based surveys were conducted in elderly Swedish individuals (aged 70 years) with serum cystatin C-estimated glomerular filtration rate <60 mL min(-1) /1.73 m2: the Uppsala Longitudinal Study of Adult Men (ULSAM) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) surveys. The present population comprised 274 men and 187 subjects (63% women) from the ULSAM and PIVUS cohorts, respectively. DESIGN: Factor analyses of serum fatty acids were used to evaluate dietary fat quality. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance (IR) and, in ULSAM, also by euglycaemic clamp. RESULTS: Factor analyses generated two fatty acid patterns of (i) low linoleic acid (LA)/high saturated fatty acid (SFA) or (ii) high n-3 polyunsaturated fatty acid (n-3 PUFA) levels. In both surveys, the low LA/high SFA pattern increased the odds of having MetS [adjusted odds ratio 0.60 [95% confidence interval (CI) 0.44-0.81] and 0.45 (95% CI 0.30-0.67) per SD decrease in factor score in the ULSAM and PIVUS surveys, respectively] and was directly associated with both IR and C-reactive protein. The n-3 PUFA pattern was not consistently associated with these risk factors. CONCLUSIONS: A serum fatty acid pattern reflecting low LA and high SFA was strongly associated with MetS, IR and inflammation in two independent surveys of elderly individuals with CKD. At present, there are no specific dietary guidelines for individuals with CKD; however, these findings indirectly support current recommendations to replace SFAs with PUFAs from vegetable oils.

Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native cardiolipin are novel biomarkers in haemodialysis patients, associated negatively with mortality.

The risk of premature death is high in haemodialysis (HD) patients. Antibodies against cardiolipin (anti-CL) are thrombogenic in diseases such as systemic lupus erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In this work we studied immunoglobulin (Ig)M anti-CL and anti-OxCL in HD-patients. We conducted an observational study with a prospective follow-up examining the relationship between anti-CL, anti-OxCL and mortality risk in a well-characterized cohort of 221 prevalent HD patients [56% men, median age 66 (interquartile range 51-74) years, vintage time 29 (15-58) months] with a mean follow-up period of 41 (20-48 months). According to the receiver operator characteristic (ROC) analysis, anti-OxCL [area under the curve (AUC) 0·62, P < 0·01], but not anti-CL (AUC 0·52, P = 0·2), is associated with mortality. In crude and adjusted Cox analysis, every log increase in anti-OxCL inversely predicted all-cause [adjusted hazard ratios (HR) 0·62 (0·43-0·89)] and CVD-related [adjusted HR 0·56 (0·32-0·98)] mortality. Patients with anti-OxCL levels below median also had increased all-cause and cardiovascular disease (CVD)-related mortality. Although anti-OxCL and anti-phosphorylcholine (PC) were related positively to each other (ρ = 0·57, P < 0·01), patients with one or two of these autoantibody levels below the median were associated with an incrementally increased death risk. Anti-OxCL were co-factor ß2-GPI-independent; anti-CL from patients with anti-phospholipid antibody syndrome were ß2-GPI-dependent, while sera from HD-patients less so. Sera from healthy donors was not ß2-GPI-dependent. Anti-OxCL IgM is ß2-glycoprotein 1 (GPI)-independent and a novel biomarker; low levels are associated with death among HD patients (and high levels with decreased risk). Combination with anti-PC increases this association. Putative therapeutic implications warrant further investigation.

Clinical determinants and mortality predictability of stearoyl-CoA desaturase-1 activity indices in dialysis patients.

BACKGROUND: Stearoyl-CoA desaturase-1 (SCD-1) converts dietary saturated fatty acids to monounsaturated fatty acids. Elevated SCD-1 activity thus signifies impaired fatty acid metabolism and excess saturated fat intake. In the general population, increased SCD-1 activity is associated with cardiovascular disease and mortality. The determinants and implications of SCD-1 activity in dialysis patients are unknown. SUBJECTS: A total of 222 dialysis patients (39% women) with prospective follow-up, median age of 57 years and an average of 12 months of dialysis. DESIGN: Fatty acid compositions in plasma phospholipids and free fatty acids (FFAs) were assessed by gas-liquid chromatography. SCD-1 activity indices were calculated as the product-to-precursor fatty acid ratio (palmitoleic acid/palmitic acid) in each fraction to reflect SCD-1 activities in the liver and adipose tissue. RESULTS: Median hepatic and adipose tissue SCD-1 activity indices were 0.016 and 0.150, respectively. In multivariate analyses, SCD-1 was positively associated with age, female sex and serum interleukin-6 level. During 18.4 (interquartile range 5.5-37.3) months of follow-up, there were 61 deaths and 115 kidney transplants. The cut-off level for high SCD-1 indices was determined by receiver operating characteristic curve analyses. In fully adjusted competing risk models, patients with high SCD-1 indices in both phospholipids and FFAs had more than twofold increased mortality risk before kidney transplantation [hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.28-4.11 and HR 2.36, 95% CI 1.38-4.03, respectively], compared with patients with low SCD-1 indices. CONCLUSIONS: Both hepatic and adipose tissue SCD-1 activity indices independently predict mortality in dialysis patients. Further studies are warranted to determine whether reducing SCD-1 activity by dietary intervention (limiting saturated fat) could improve survival in dialysis patients.

Visceral obesity assessed by computed tomography predicts cardiovascular events in chronic kidney disease patients.

BACKGROUND AND AIM: Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Although there is emerging evidence that excess visceral fat is associated with a cluster of cardiometabolic abnormalities in these patients, the impact of visceral obesity evaluated by a gold-standard method on future outcomes has not been studied. We aimed to investigate whether visceral obesity assessed by computed tomography was able to predict cardiovascular events in CKD patients. METHODS AND RESULTS: We studied 113 nondialyzed CKD patients [60% men; 31% diabetics; age 55.3 ± 11.3 years; body mass index (BMI) 27.2 ± 5.3 kg/m(2); estimated glomerular filtration rate (GFR) 33.7 ± 13.6 ml/min/1.73 m(2)]. Visceral and subcutaneous abdominal fat were assessed by computed tomography at L4-L5. Visceral to subcutaneous fat ratio >0.55 (highest tertile cut-off) was defined as visceral obesity. Cardiovascular events including acute myocardial infarction, angina, arrhythmia, uncontrolled blood pressure, stroke and cardiac failure were recorded during 24 months. Cardiovascular events were 3-fold higher in patients with visceral obesity than in those without visceral obesity. The Kaplan-Meier analysis indicated that patients with visceral obesity had shorter cardiovascular event-free time than those without visceral obesity (P = 0.021). In the univariate Cox analysis, visceral obesity was associated with higher risk of cardiovascular events (hazard ratio = 3.4; 95% confidence interval = 1.1-10.5; P = 0.03). The prognostic power of visceral obesity for cardiovascular events remained significant after adjustments for sex, age, diabetes, previous cardiovascular disease, smoking, sedentary lifestyle, BMI, GFR, hypertension, dyslipidemia and inflammation. CONCLUSION: Visceral obesity assessed by computed tomography was a predictor of cardiovascular events in CKD patients.

The newly identified anorexigenic adipokine nesfatin-1 in hemodialysis patients: Are there associations with food intake, body composition and inflammation?

Nesfatin-1 is a recently identified anorexigenic peptide that has been implicated in appetite regulation, weight loss and/or malnutrition. Anorexia and malnutrition are common features of chronic kidney disease (CKD) that predispose patients to worse outcomes. However, the reasons for the occurrence of anorexia in CKD patients are not fully elucidated. The aim of this study was to investigate the association between nesfatin-1 and protein intake and body composition in patients undergoing hemodialysis (HD). Twenty five HD patients from a private Clinic in Rio de Janeiro, Brazil were studied and compared with 15 healthy subjects that were matched for body mass index (BMI), % body fat mass (by anthropometrics) and age. Appetite was measured using a specific questionnaire, and food intake was evaluated based on 3-day food records. Nesfatin-1 levels were measured by ELISA and leptin, TNF-α and IL-6 levels were determined by a multiplex assay kit. Serum nesfatin-1 levels did not differ between HD patients (0.16±0.07ng/mL) and healthy subjects (0.17±0.10ng/mL). Nesfatin-1 levels showed significant negative correlations with protein intake (r=-0.42; p=0.03), but did not associate with inflammatory markers or appetite scores. Combining patients and controls, we observed positive correlations with BMI (r=0.33; p=0.03), % body fat (r=0.35; p=0.03), leptin (r=0.45; p=0.006) and the triceps skinfold thickness (r=0.36; p=0.02). In multivariate analysis % body fat was the main determinant of nesfatin-1 variance. In conclusion, nesfatin-1 levels did not differ between HD patients and healthy subjects and negatively correlated with protein intake. This pathway is likely not dysregulated in uremia.

The possible role of nesfatin-1 on appetite regulation in hemodialysis patients.

Studies on appetite hormones in chronic kidney disease (CKD) patients appear of interest since these compounds may be implicated in reduced appetite, loss of weight and/or malnutrition. Anorexia seems to be related to many hormones that act in central nervous system, like leptin, obestatin and others, and more recently, was discovered a hypothalamus secreted protein that conduces to a decrease on food intake and to an increase on energetic waste, called nesfatin-1. This peptide has been studied in diabetes, mean arterial pressure and cardiovascular function, anxiety- and/or fear-related responses and inflammation, but there are no studies about a possible relationship with CKD. Therefore, considering the negative impact of anorexia and malnutrition in morbidity and mortality of CKD patients and the interest in new treatments findings for dialysis population, this review will discuss recent information about nesfatin-1 and its possible role in CKD patients.

The effect of immunosuppressive treatment on arterial stiffness and matrix Gla protein levels in renal transplant recipients.

INTRODUCTION: Arterial stiffness is a risk marker for cardiovascular events. In this study we aimed to compare the effect on calcineurin inhibitors (CNI) and mammalian Target of Rapamycine inhibitors (mTORi) on arterial stiffness in renal transplant patients. PATIENTS AND METHODS: 81 renal transplant patients under CNI-based or mTORi-based protocol for at least 6 months were included in the study. Arterial stiffness was measured by using the SphygmoCor device (AtCor Medical, Sydney, Australia). Vitamin K-dependent, calcification inhibitor matrix Gla protein (MGP) concentrations were quantified by ELISA methods (Biomedica, Vienna, Austria). RESULTS: 34 patients were on mTORi-based and 47 on CNI-based immunosuppression. Mean age was 37.9 ± 10.8 (18 - 71) years and 45% were female. Age, gender, graft functions and follow-up period of the groups were similar. Augmentation index was 15.2 ± 12.6% in CNI and 18.8 ± 14.0% in mTORi groups (p > 0.05). There was no difference regarding carotid-femoral pulse wave velocity between groups. Arterial stiffness was positively correlated with age, total cholesterol, LDL cholesterol, mean arterial pressure (MAP) and proteinuria. MGP levels were higher in the mTORi group but were not predictors for carotid-femoral pulse wave velocity. CONCLUSION: Rather than specific immunosuppressive drug effects, conventional risk factors, blood pressure and proteinuria are the most important predictors for arterial stiffness in renal transplant patients.

Plasma osteoprotegerin, arterial stiffness, and mortality in normoalbuminemic Japanese hemodialysis patients.

UNLABELLED: A high circulating osteoprotegerin (OPG) level may be a risk factor for vascular calcification and mortality in hemodialysis patients. OPG and pulse wave velocity (PWV) were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients who were prospectively followed for 6 years. In long-term normoalbuminemic Japanese hemodialysis patients, OPG levels were strongly linked with both arterial stiffness and worse outcome. INTRODUCTION: A high circulating OPG level is reported to be a risk factor for vascular calcification and mortality in Western chronic kidney disease (CKD) patients but it is not known if this is true for Japanese CKD patients, where a different risk profile may operate. METHODS: OPG and PWV were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients (median age 62 years) who were prospectively followed for 6 years. RESULTS: OPG levels were associated in multivariate analysis with age, dialysis vintage, history of cardiovascular disease (CVD) and parathyroid hormone levels. C-reactive protein levels did not correlate with OPG. Patients with clinical history of CVD had significantly higher OPG levels and OPG levels were positively correlated to PWV, an index of arterial stiffness. These associations were independent of age, sex, dialysis vintage, and diabetes. During the follow-up period, 40 deaths, including 25 cardiovascular deaths, were recorded. In crude analysis, each unit of increase in OPG was associated with increased all-cause (hazard ratios 1.14, 95% confidence interval 1.08-1.20) and CVD mortality (1.14 [1.07-1.21]), which persisted after adjustment for age, sex, dialysis vintage, diabetes, and baseline CVD (1.12 [1.05-1.19] and 1.11 [1.02-1.19], all-cause and CVD mortality, respectively). CONCLUSIONS: In long-term normoalbuminemic Japanese hemodialysis patients, with low prevalence of inflammation, OPG levels were strongly linked with both arterial stiffness and worse outcome.

Increased expression of pro-inflammatory genes in abdominal subcutaneous fat in advanced chronic kidney disease patients.

OBJECTIVES: Low-grade systemic inflammation, oxidative stress and peripheral insulin resistance are intimately associated and contribute to the increased risk of cardiovascular complications in advanced chronic kidney disease (CKD). Because altered adipose tissue activities have previously been linked to pathophysiological processes in various inflammatory and metabolic diseases we hypothesized that the uraemic milieu in patients with CKD may interact with the adipose tissue, provoking an unfavourable shift in its transcriptional output. DESIGN: Twenty-one adipokine mRNAs were quantified in abdominal subcutaneous adipose tissue (SAT) biopsies and serum/plasma concentrations of inflammatory markers and related protein products were measured. SETTING: The study was conducted at the Karolinska University Hospital, Huddinge, and Karolinska Institutet, Stockholm, Sweden. SUBJECTS: Thirty-seven patients with CKD [15 women, median 58 (interquartile range 49-65) years] and nine nonuraemic individuals [four women, age 62 (45-64) years] were recruited prior to initiation of peritoneal dialysis catheter insertion or elective hernia repair/laparoscopic cholecystectomy, respectively. RESULTS: Even after correction for body mass index, SAT from patients showed a significant upregulation of inflammatory pathway genes interleukin 6 (3.0-fold, P=0.0002) and suppressor of cytokine signalling 3 (2.5-fold, P=0.01), as well as downregulation of leptin (2.0-fold, P=0.03) and the oxidative stress genes uncoupling protein 2 (1.5-fold, P=0.03) and cytochrome b-245, alpha polypeptide (1.5-fold, P=0.005), in relation to controls. CONCLUSIONS: These gene expression differences suggest that inflammatory and oxidative stress activities may be important features of the intrinsic properties of uraemic adipose tissue, which may have significant effects on the uraemic phenotype.

Adiponectin in chronic kidney disease has an opposite impact on protein-energy wasting and cardiovascular risk: two sides of the same coin.

Adiponectin, an anti-inflammatory, anti-atherogenic and insulin sensitizing adipokine exists in several isoforms in the circulation. In patients with chronic kidney disease (CKD), circulating levels of total as well as high-molecular-weight adiponectin are elevated. In contrast to initial studies, several recent and larger studies on outcomes do not support a protective effect of high adiponectin on cardiovascular disease (CVD) and overall mortality in CKD patients. Paradoxically, high adiponectin predicts increased overall and cardiovascular mortality in CKD patients. This effect seems unrelated to a direct effect of adiponectin, but rather due to a process of protein-energy (PEW) wasting. This review summarizes recent conflicting findings on adiponectin in relation to outcomes and discusses the pathophysiologic roles of adiponectin in PEW, insulin resistance and vascular injuries of CKD patients.